Researchers at UAB have designed simplified biostructures that mimic natural enzymes, capable of carrying out two distinct and reversibly regulated activities thanks to a unique combination of structural and functional properties. The strategy used opens the door to the creation of “smart” nanomaterials with tailored combinations of catalytic functions.
There is growing interest in synthetic systems that can implement biochemical reactions without the need for the complex structures that characterize enzymes in their components. Self-assembly of peptides – which are smaller molecules of proteins – is one of the most explored approaches due to their biocompatibility and how to control their structural and functional properties.
Researchers from the Institute of Biotechnology and Biomedicine at the Autonomous University of Barcelona (IBB-UAB) recently designed one of the smallest simulated enzyme structures ever. These peptides consist of 7 to 9 amino acids that are automatically assembled to form stable amyloid fibers and solid hydrogels, which are harmless to cells.
Peptides consist of only two types of water-soluble amino acids (tyrosine and histidine), and are a binary code that contains all the information needed to form nanostructures. In addition, they are reversible and can carry out two distinct and uncorrelated stimulating activities.
The researchers were able to create a simpler system that could better control enzymatic activity and, for the first time, a structure in which the same amino acids providing catalytic activity also contribute to the formation of the structure of macromolecules. In previous studies, these capabilities were separated in different regions of the molecule, resulting in longer peptides and / or peptides with a single function.
“The opposite in the question is that the catalytic activity of fibers and hydrogels can only be achieved when the peptides self-assemble,” explains Salvador Ventura, study coordinator. “The strategy we used defines the foundations for creating materials with ‘smart’ nanostructures, with specially designed sets of catalytic functions for a number of practical applications.”
To date, the majority of designer mini-peptides lack one of the most important abilities of natural enzymes: the ability to reverse-regulate their activity. In this study, the researchers were able to control the aggregation capacity, and this allows for alternation between the active and inactive forms with small changes in the pH.
In addition, the new peptides have properties that natural enzymes do not possess, because they only perform catalytic activities. Now, peptides comprise two different types of activities (aqueous and electrical stimulation) which can be performed simultaneously or alternately. In any other case, this would require two structurally different synthetic enzymes that would be hundreds of times larger and more expensive.
Another characteristic of these new synthetic enzymes that researchers are referring to is the spontaneity of self-assembly, which means that there is no need for additional chemical reagents or the use of heat, which could be toxic or have drastic effects on their structure. .
More efficiency and economy
Hydrogels and amyloid-like fibers allow the generation of rigid microscopic reactors that are more efficient and economical, where the final product of the reaction can be easily separated from the synthetic enzyme.
“The large molecular structures that we were able to create may have important applications in microfluidics, as well as in drug delivery, as they can encapsulate a drug in its pooled state and release it in a specific way, once the correct cell context is achieved, simply by disassembling,” says Salvador Ventura.
Salvador Ventura is the Head of the Protein Folding and Compatibility Pathology Group at IBB. “We started the research lines in nanotechnology only three years ago, but our knowledge of the molecular mechanism of protein assembly into amyloid structures helped us develop new functional and synthetic nanomaterials with properties that could not be achieved using natural peptides or proteins,” he says.
The study was recently published in the journal ACS stimulator, Included the participation of researchers from IBB and from UAB’s chemistry and biochemistry departments and molecular biology (Salvador Ventura, Marta Díaz Caballero, Susana Navarro, Mariona Sodobi and Luis Rodriguez Santiago); From the Institute of Materials Science in Barcelona (ICMAB-CSIC) (Francesc Teixidor and Miquel Nuez-Martínez) and from the Center for Collaborative Research in Biological Sciences (CIC bioGUNE) (Francesca Peccati).